The objective of the proposed research is to delineate the mechanisms by which glia interact with their extracellular environment, specifically with regard to neurotransmitters. Secondly, it is to determine the significance of this interaction in maintaining the composition of the extracellular space. Finally, it is to evaluate effects of gliosis on these normal regulatory processes. The goals can be met by determining characteristics of uptake, metabolism, and release of neurotransmitters in cultured glial cells, and in brain homogenates, slices and intact brain from normal and gliotic preparations. Neurotransmitter uptake systems will be selectively identified and characterized by their kinetic properties, ionic and energy requirements and substrate, pharmacologic and stereo specificity. Neurotransmitter transport properties will initially be characterized in cultured glial cells and then compared in normal and gliotic tissue. The metabolism and release of putative neurotransmitters in these preparations will be evaluated using radiolabeled precursors and determining tissue levels, specific activities and release of the transmitter substances, particularly for the amino acid transmitter candidates. The proposed research will increase our understanding of glial cell function and should also clarify the contribution of gliosis to the neural dysfunction seen in gliotic conditions includig certain forms of epilepsy.